1. Field of the Invention
This invention relates generally to the fields of pharmacology and cardiology. In particular, the present invention provides methods for altering the rate of depolarization and repolarization of the ventricles of the heart. More specifically, this invention provides methods for the use of certain carbamate compounds to therapeutically alter the QT interval.
2. Description of the Related Art
The beating of the heart is a precisely controlled event that relies on the exact coordination of the atrial and ventricular contractions to obtain maximum pumping efficiency. The regularly spaced waves of myocardial excitation and contraction originate in the SA node and spread throughout the heart in well-defined manner. The electrocardiogram (ECG or EKG) provides valuable information about functional state and health and reflects the summation of all of the electrical activity in the heart. Electrical leads are placed on the body in specific places and the electrical activity resulting from heart depolarization, and repolarization, is recorded by each lead.
The size and direction of the ECG depends upon the direction that the electrical current is flowing, and on the magnitude of the muscle that is depolarized. Therefore, when the atria depolarize (and contract) the wave is smaller compared to when the ventricles contract. This is because the mass of atria are so much smaller then the ventricles. The repolarization of the ventricles (the T-wave) is in the same direction (positive) as the ventricular depolarization. This is because the ventricles depolarize from the inside to the outside (endocardium to epicardium), while repolarization occurs from the outside to the inside (epicardium to endocardium).
P-Wave: The cardiac cycle begins with the spontaneously firing cells in the SA node reaching threshold and generating action potentials. This produces a wave of depolarization that spreads to the left and downward though the atrial mass. The atria that were hyperpolarized suddenly become depolarized and the ECG records a positive deflection.
When the entire atria becomes depolarized the wave returns to 0. Then there is a delay of about 0.1 seconds, while the electrical current is passing through the AV node. When the AV node is depolarized it triggers depolarization of the Purkinje fibers. This tissue spreads the electrical current throughout the ventricles so that depolarization occurs across the entire ventricle simultaneously.
Next the ventricles depolarize resulting in the QRS complex. The 3 peaks are due to the way that current spreads through the ventricles, from inside to outside and because the tissue mass is greater on the left side then the right side. When the ventricles are completely depolarized the ORS complex is finished.
T-Wave: Repolarization of the ventricle leads to the T wave. Although the ventricles are repolarizing the T wave is still positive. This is because the heart repolarizes from outside to inside, the opposite direction of depolarization (it was inside to outside). This is the end of the cardiac cycle.
The QT interval is the time between the beginning of the QRS complex and the end of the T wave. This interval represents the time required for the depolarization and repolarization of the ventricle. The duration of the depolarization and repolarization of the ventricle can be affected by many conditions including; genetic variation, cardiac disease, electrolyte balance and many otherwise useful drugs. In many cases, prolongation of the QT interval beyond a certain point, by any of these conditions, can result in a dangerous situation in which the ventricle is at risk for possibly fatal arrhythmias. Thus, methods to control the duration of the QT interval and especially to shorten it, are needed.